Despite evidence that mechanical loads can induce diaphyseal bone growth, there is little consensus about how, and to what extent, strain affects human skeletal phenotype. This project tests a mechanism of mechanotransduction in bone that may underlie variation in human skeletal robusticity. One hypothesis of particular relevance to humans is that hormones, particularly estradiol (E2) and its receptor, estrogen receptor alpha (ER-a), affect mechanotransduction in osteoblasts. Previous experiments demonstrate that E2 increases osteogenic responses to loading, but the mechanism involved is unclear. This project tests the hypothesis that E2 affects osteogenesis by upregulating ER-a, making osteoblasts more sensitive to mechanical loading.
To test this hypothesis, 36 ovarie c-tomized C57BL/6J mice were divided into normal, high, and low E2 treatment groups implanted with 0.25 mg, 2.5 mg, or placebo E2 pellets. Half of the mice in each E2 group were fed normal mouse pellets, while half were fed a soft paste made from the same pellets. Results indicate that in the lateral mandibular corpus, hard diet animals exhibit 260% (high E2), 21% (low E2), and 82% (placebo) more growth than soft diet animals (p=0.01 to 0.03). In situ hybridization shows that ER-a is expressed in mandibular osteoblasts and hypertrophic chondrocytes, and expression appears to increase with increasing E2 dose. Evidence that E2 level affects diaphyseal bone growth via regulation of ER-a may help explain patterns of variation in human skeletal robusticity.